Review Reports

Reviewer’s comment

Author’s response

Reviewer 1

The reviewer systematically addressed main methodological issues including study design, randomization, outcome measurement, and data reporting.

Thank you for your comment.

Points out that cough severity categories may be subjective and not formally validated.

Thank you for your comment.

I agree with the author in terms of warning in comparing results with trials that differ in design, population, or endpoints. However, the reviewer does not perform any statistical re-analysis of the original data. The critique is based on reported methods and results.

Thank you for your comment. Statistical re-analysis was beyond the scope of this letter and the data from the original study are not available to permit such analyses. As stated in the introduction (lines 22–24), the purpose of the letter was to provide an appraisal of the study design, randomization strategy, and analytical approach. No amends have been made to the letter.

The review seems to focus mostly on methodology but does not deeply engage with the clinical relevance of herbal therapies for acute bronchitis, which is often self-limiting.

Thank you for your comment. A detailed discussion of the clinical relevance of herbal therapies is beyond the scope of this letter, which aims to appraise the methodology of the original trial. The following sentence has been added to the introduction (lines 11–13) to briefly touch on the clinical relevance of herbal therapies for acute bronchitis: “Although bronchitis is a self-limiting illness, patients may benefit from herbal therapies, which have been shown to reduce cough severity and symptom burden [2].”

The reviewer questions the BSS MCID but does not propose an alternative or reference a validated tool for acute bronchitis.

Thank you for your comment. The following sentence has been added to the letter (lines 57–59): “By contrast, the Visual Analog Scale (VAS) and Leicester Cough Questionnaire (LCQ-acute) both have validated MCIDs in acute cough and may have been more valuable primary outcome measures [9].”

The call for “larger-scale, double-blinded, randomized controlled trials” is standard but may not always be feasible for herbal comparative studies.

Thank you for your comment.

The author underlined that, while unequal randomization ratios (like 3:2:2) can sometimes be used in trials, no rationale was provided by the original authors. In clinical research, deviations from balanced randomization (e.g., 1:1:1) must be justified. If one treatment is hypothesized to be better, why are fewer patients assigned to it? Without explanation, it may seem like the sponsor’s product was prioritized. The author should explain it more in detail.

Thank you for highlighting this important point. The following sentence has been added to the letter (line 41–42) to clarify that the sponsor’s product may have been prioritized: “Without explanation, the unequal allocation may imply that the sponsor’s product (ivy extract) was prioritized.”

Given that the trial has already been conducted, a major revision is recommended.

Thank you for your comment. The letter has been revised as suggested.

Reviewer 2

The introduction should provide a more detailed description of the design and preliminary findings of the previous experiment before the critique.

Thank you for your comment. The introduction has been revised to briefly summarize the trial design and key findings of the original trial (lines 13–17): “In this trial, 325 adult patients were randomized 3:2:2 to receive ivy, ivy/thyme, or thyme/primrose for 7 days, followed by a 7-day observation period. The primary endpoint was the assessment of non-inferiority, and the secondary endpoint was the assessment of superiority of ivy compared to each combination therapy, regarding change from baseline in Bronchitis Severity Score (BSS) at Day 7.”

Clear guidelines should be provided regarding participant selection methods, blinding procedures, and management practices for future research on herbal medicines for acute bronchitis, as well as the analysis of outcomes and necessary reporting criteria.

Thank you for your comment. Relevant reference to guidelines has been included where appropriate, including guidance on the design, conduct, and analysis of open-label randomized trials (reference 3, line 29) and on the reporting of randomized trials (reference 11, line 70). No amends have been made to the letter.

In conclusion, cross-trial comparisons should not be over-interpreted. A short phrase should make it clear what level of evidence the current study can provide (for example, hypothesis-generating only) and how future double-blind, sufficiently randomized controlled trials can fill in the gaps that have been found. These improvements would make the letter more useful for healthcare providers.

Thank you for your comment. The level of evidence the original trial can provide (i.e., hypothesis-generating) is stated in lines 20 and 95. The conclusion has been revised to reinforce the value of future double-blind, randomized controlled trials (lines 97–99): “Such studies would ensure that the observed effects are substantiated without bias from the open-label design and unequal randomization.”

The English could be improved to more clearly express the research.

Thank you for your comment. The English has been improved where possible.